a) Field of the invention
This invention relates to a production process of rubber plugs, and more specifically to a process for producing rubber plugs to be used with medical containers or medical devices, each of said rubber plugs being reduced in the number of insoluble fine particles attracted on a surface of the rubber plug while pyrogen substances having been removed (or deactivated) on and in the vicinity of the surface of the rubber plug. The term xe2x80x9cinsoluble fine particlesxe2x80x9d means fine particles insoluble in liquid medicine and will hereinafter be referred to simply as xe2x80x9cfine particlesxe2x80x9d.
b) Description of the Related Art
Rubber plugs made of butyl rubber, chlorinated butyl rubber or the like have been used for many years as opening stoppers for medical containers, such as bottles for infusions, vials and bottles for medicaments and experimental reagents, and vials and bottles for injections, and also for medical devices such as combination container-and-syringes.
A variety of rubber plugs for medical containers or medical devices, such as those described above, are generally obtained through a kneading step, a forming step (vulcanization step) and a punching step (pressing step). The kneading step comprises adding a vulcanizing agent and other additives to feed rubber and then kneading the resulting mixture to prepare a vulcanizable, mixed rubber compound. The forming step comprises forming the vulcanizable, mixed rubber compound into a burr-like sheet, which is provided with rubber plugs of a predetermined shape formed thereon, by compression molding or injection molding and then vulcanizing the burr-like sheet. The punching step, on the other hand, comprises individually cutting the rubber plugs apart from the formed sheet.
The rubber plugs, which have been cut apart, are processed through a washing step, which make use of chemical reagents (alkali, acid, and the like) and high-quality water, and a drying step. The thus-obtained rubber plugs are subjected to a final inspection step, in which the resultant rubber plugs are inspected for external appearances and any attracted materials, and further to a final visual inspection and a sanitary test to determine whether or not they meet various official standards specified in xe2x80x9cTests for Rubber Plugs to Be Used with Infusionsxe2x80x9d in the first addendum of the thirteenth edition of the Pharmacopoeia of Japan. Those determined to meet the official standards are packed and shipped. Concerning sanitary requirements for rubber plugs, specification values are set not only in the Pharmacopoeia of Japan but also in the Pharmacopoeias in various European and American countries.
Rubber plugs, to which the present invention can be applied, are produced using desired one of various rubbery polymers as a primary material. As a characteristic property of a high-molecular substance, however, a rubbery polymer tends to have a static charge by friction. In the course of production of rubber plugs, formed rubber plugs are successively conveyed to subsequent steps by belt conveyors or the like. During these conveyance, rubber plugs are brought into contact with each other within a transportation container. The rubber plugs are therefore electrostatically charged, leading to a problem that in each step, contaminants such as fine particles, lint and hairs in an environment are attracted onto surfaces of the rubber plugs.
Especially when a material attracted on the rubber plugs is in the form of fine particles, mixing of such fine particles into medicaments (powdery or liquid medicines) in medical devices, such as syringes, making use of the rubber plugs is unavoidable irrespective of the amount of the fine particles. Injection of a medicament, such as an injectable preparation, with such fine particles mixed therein into the human body involves a potential danger that the fine particles in the medicament may develop a serious problem detrimental to the human life such as clotting of a blood vessel in the human body. In the Pharmacopoeia of each country, specification limits are hence regulated regarding the size and number of fine particles in an injectable preparation per unit volume of the injectable preparation. In Japan, a test for insoluble foreign substances in an injectable preparation and a test for fine particles in an injectable preparation are specified as general tests in the first addendum of the thirteenth edition of the Pharmacopoeia. Likewise, they are also specified as general tests in the Pharmacopeia of the United States of America. These tests in the individual countries specify the above-described specification limits.
Concerning rubber plugs, no specification value is set for fine particles attracted on the rubber plugs in the above-described xe2x80x9cTests for Rubber Plugs to Be Used with Infusionsxe2x80x9d of the Pharmacopoeia of Japan. In view of the above-described circumstances, however, the Applicant is performing at its own volition an inspection for fine particles attracted on rubber plugs. As a reduction in the number of fine particles attracted on a rubber plug leads to a decrease in the number of fine particles in an injectable preparation, there is an ever-increasing demand from drug makers toward rubber plugs with fewer fine particles attracted thereon.
Attraction of fine particles onto rubber plugs in the course of their production is attributed to frictional electrification of the rubber plugs as described above. In attempts to reduce attraction of fine particles, measures have hence been taken including cleaning of air in a working environment, lessening of mutual friction of rubber plugs, omission of any step in which a worker touches rubber plugs by hand. No satisfactory results, however, have been obtained yet.
An object of the present invention is, therefore, to provide a production process for rubber plugs to be used with medical containers or medical devices, which makes it possible to reduce attraction of fine particles (which is generally called xe2x80x9cfine particle contaminationxe2x80x9d).
The present inventors have proceeded with an extensive investigation to achieve the above-described object. As a result, it has been found that improvements in washing and drying steps for rubber plugs make it possible to reduce attraction of fine particles onto the rubber plugs, leading to the completion of the present invention.
To achieve the above-described object, the present invention provides a process for producing rubber plugs, which are to be used with medical containers or medical devices, by forming a vulcanizable, mixed rubber compound and vulcanizing a resultant formed rubber compound, which comprises the following additional consecutive steps:
1) treating the rubber plugs with steam of high temperature and high pressure;
2) treating the rubber plugs in an aqueous solution which has been adjusted to be acidic;
3) rinsing the rubber plugs with high-quality water;
4) washing the rubber plugs with a shower of dust- and germ-free water; and
5) drying the rubber plugs by at least one of far infrared radiation and high frequency heating.
According to the present invention, rubber plugs reduced to an extremely low level in the number of fine particles attracted thereon are provided for use with medical containers or medical devices.